Sonodynamic therapy, the ultrasound dependent enhancement of cytotoxic activities of certain compounds (sonosensitizers) in studies with cells in vitro and in tumor bearing animals, is reviewed. The attractive features of this modality for cancer treatment emerges from the ability to focus the ultrasound energy on malignancy sites buried deep in tissues and to locally activate a preloaded sonosensitizer. Possible mechanisms of sonodynamic therapy include generation of sonosensitizer derived radicals which initiate chain peroxidation of membrane lipids via peroxyl and/or alkoxyl radicals, the physical destabilization of the cell membrane by the sonosensitizer thereby rendering the cell more susceptible to shear forces or ultrasound enhanced drug transport across the cell membrane (sonoporation). Evidence against the role of singlet oxygen in sonodynamic therapy is discussed. The mechanism of sonodynamic therapy is probably not governed by a universal mechanism, but may be influenced by multiple factors including the nature of the biological model, the sonosensitizer and the ultrasound parameters. The current review emphasizes the effect of ultrasound induced free radicals in sonodynamic therapy.

A major limitation in determining the effects of ultrasound frequency in sonochemistry in relation to cavitation is that no reliable relationship exists between the energy supplied to the system and the energy converted by the cavitation process in producing a sonochemical effect. However, the current study presents a frequency effect that is independent of the energy supplied to the system. Spin-trapping of secondary carbon radicals with 3,5-dibromo-4-nitrosobenzenesulfonic acid-d 2 (DBNBS-d 2 ) and electron paramagnetic resonance (EPR) have been used to determine the relative ability of two nonvolatile surfactants [sodium 1-pentanesulfonic acid (SPSo) and sodium dodecyl sulfate (SDS)] to scavenge • H atoms and • OH radicals at the gas/solution interface of cavitation bubbles. The results obtained at 354 and 1057 kHz are compared to those observed previously at 47 kHz (Sostaric, J. Z.; Riesz, P. J. Am. Chem. Soc. 2001, 123, 11010-11019). At particular bulk surfactant concentrations, both surfactants reached a limiting plateau value in radical scavenging ability. At 354 kHz (and 47 kHz), the magnitude of this plateau was greater for SPSo compared to that for SDS. However, at 1057 kHz, no difference in the plateau value was observed between SPSo and SDS. Decreasing the ultrasound intensity at constant frequency during the sonolysis of SPSo and SDS resulted in a decrease in the -• CH-radical yield. However, there was no change in the relative plateau yield of -• CH-radicals between SPSo and SDS. Thus, at plateau concentrations, the relative ability of these n-alkyl chain surfactants to scavenge radicals at the gas/solution interface of cavitation bubbles depends on the frequency of sonolysis but is independent of ultrasound intensity. The results were interpreted in terms of a decrease in the rate of change of the surface area of "high-energy-stable cavitation bubbles" at higher frequencies. This would affect the relative adsorption and hence radical scavenging efficiencies of SPSo and SDS at the gas/solution interface of these types of cavitation bubbles.

The surfactant properties of solutes play an important role in the sonochemistry and sonoluminescence of aqueous solutions. Recently, it has been shown, for relatively low molecular weight surfactants, that these effects can be correlated with the Gibbs surface excess of the solute. In the present study we investigate whether this correlation is valid for relatively high molecular weight surfactants and the mechanisms of surfactant decomposition during sonolysis. Sonolysis of argon-saturated aqueous solutions of nonvolatile surfactants [n-alkanesulfonates, n-alkyl sulfates, n-alkylammoniopropanesulfonates (APS), and poly(oxyethylenes) (POE)] was investigated by EPR and spin-trapping with 3,5-dibromo-4-nitrosobenzenesulfonate. Secondary carbon radicals (-.CH-), formed by abstraction reactions, were observed for all surfactants that were sonicated. The yield of primary carbon (-.CH(2)) and methyl (.CH(3)) radicals that are formed by pyrolysis is greatest for the zwitterionic (i.e., APS) and nonionic surfactants (i.e., POE). The yield of (-.CH-) radicals was measured following sonolysis of n-alkyl anionic surfactants [sodium pentanesulfonate (SPSo), sodium octanesulfonate (SOSo), sodium octyl sulfate (SOS), and sodium dodecyl sulfate (SDS)]. In the concentration range of 0-0.3 mM, the -.CH- radical yield increases in the order SDS approximately equal to SOS approximately equal to SOSo > SPSo. At higher concentrations, a plateau in the maximum (-.CH-) radical yield is reached for each surfactant, which follows the order SPSo > SOS approximately equal to SOSo > SDS; i.e., the radical scavenging efficiency increases with decreasing n-alkyl chain length. A similar trend was observed for the .CH(3) yield following sonolysis of a homologous series of n-alkyl APS surfactants. The results show that the Gibbs surface excess of certain nonvolatile surfactants does not correlate with the extent of decomposition following sonolysis in aqueous solutions. Instead, the decomposition of surfactants depends on their chemical structure and their ability to equilibrate between the bulk solution and the gas/solution interface of cavitation bubbles.